The syndrome of familial medullary thyroid carcinoma is inherited as an autosomal dominant trait and is characterized by the development of bilateral and multicentric C-cell and adrenal medullary tumors. Sequential clinical screening studies both for determination of calcitonin and catecholamine levels in these kindreds, combined with correlative pathological analyses, have led to the concept that both these tumors are preceded by relatively long preneoplastic phases of C-cell and adrenal medullary hyperplasia. The human tumor system, together with a series of similar proliferative disease processes in experimental animals, provides a unique source of material to study the early phases of neoplastic growth and to delineate the differences between physiological and preneoplastic (pathological) hyperplasia. A number of parameters which have been associated with abnormal cell growth, including alterations in cell junctions (desmosomes) and abnormalities in the basal lamina, will be investigated with morphometric techniques, and will be correlated with the progressive phases of preneoplastic and neoplastic development. Employing antisera monospecific for fragments of calcitonin M, immuno-electron microscopic studies will be undertaken to directly correlate tissue and serum calcitonin heterogeneity with secretory granule morphology and with the phases of preneoplastic or neoplastic growth. These studies may provide an opportunity to assess aberrations of hormonal synthetic and secretory function with regard to heterogeneity of polypeptide hormones during the process of neoplastic transformation.